2022 Vol. 13, No. 3

Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. In this issue, Ma et al. utilize powerful genetic approaches in Caenorhabditis elegans to uncover evolutionarily conserved mitochondrial exporters and importers that control mitochondrial Zn2+ levels. They provide molecular insights into the mechanisms that control appropriate mitochondrial Zn2+ levels required for maintenance of mitochondrial homeostasis. The cover image shows that reinforced expression of human SLC25A25 (EGFP-SLC25A25, green), a mitochondrial Zn2+ importer, induced abnormally enlarged mitochondria (Mito Tracker DR staining, red) by elevating mitochondrial Zn2+ in HeLa cells.

Youheng Tang, the pioneering founder of South China Agricultural University
Yuan Chen, Alan W. Adame, Ge-Zhi Chen, Yuanyuan Meng
2022, 13(3): 157-162. doi: 10.1007/s13238-020-00815-6
Governing glutaminolysis by regulation of glutaminase succinylation
Qingxia Ma, Hongfei Jiang, Leina Ma, Ying Meng, Dong Guo, Yingying Tong, Zhimin Lu
2022, 13(3): 163-166. doi: 10.1007/s13238-021-00897-w
Cancer biology deciphered by single-cell transcriptomic sequencing
Yanmeng Li, Jianshi Jin, Fan Bai
2022, 13(3): 167-179. doi: 10.1007/s13238-021-00868-1
Tumors are complex ecosystems in which heterogeneous cancer cells interact with their microenvironment composed of diverse immune, endothelial, and stromal cells. Cancer biology had been studied using bulk genomic and gene expression profiling, which however mask the cellular diversity and average the variability among individual molecular programs. Recent advances in single-cell transcriptomic sequencing have enabled a detailed dissection of tumor ecosystems and promoted our understanding of tumorigenesis at single-cell resolution. In the present review, we discuss the main topics of recent cancer studies that have implemented single-cell RNA sequencing (scRNA-seq). To study cancer cells, scRNA-seq has provided novel insights into the cancer stem-cell model, treatment resistance, and cancer metastasis. To study the tumor microenvironment, scRNA-seq has portrayed the diverse cell types and complex cellular states of both immune and non-immune cells interacting with cancer cells, with the promise to discover novel targets for future immunotherapy.
Research Article
A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis
Tengfei Ma, Liyuan Zhao, Jie Zhang, Ruofeng Tang, Xin Wang, Nan Liu, Qian Zhang, Fengyang Wang, Meijiao Li, Qian Shan, Yang Yang, Qiuyuan Yin, Limei Yang, Qiwen Gan, Chonglin Yang
2022, 13(3): 180-202. doi: 10.1007/s13238-021-00881-4
Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.
Restoration of FMRP expression in adult V1 neurons rescues visual deficits in a mouse model of fragile X syndrome
Chaojuan Yang, Yonglu Tian, Feng Su, Yangzhen Wang, Mengna Liu, Hongyi Wang, Yaxuan Cui, Peijiang Yuan, Xiangning Li, Anan Li, Hui Gong, Qingming Luo, Desheng Zhu, Peng Cao, Yunbo Liu, Xunli Wang, Min-hua Luo, Fuqiang Xu, Wei Xiong, Liecheng Wang, Xiang-yao Li, Chen Zhang
2022, 13(3): 203-219. doi: 10.1007/s13238-021-00878-z
Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABAA receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Exosomes from antler stem cells alleviate mesenchymal stem cell senescence and osteoarthritis
Jinghui Lei, Xiaoyu Jiang, Wei Li, Jie Ren, Datao Wang, Zhejun Ji, Zeming Wu, Fang Cheng, Yusheng Cai, Zheng-Rong Yu, Juan Carlos Izpisua Belmonte, Chunyi Li, Guang-Hui Liu, Weiqi Zhang, Jing Qu, Si Wang
2022, 13(3): 220-226. doi: 10.1007/s13238-021-00860-9
Correction to: Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model
Xiaoyan Xu, Yaqin Sun, Xufeng Cen, Bing Shan, Qingwei Zhao, Tingxue Xie, Zhe Wang, Tingjun Hou, Yu Xue, Mengmeng Zhang, Di Peng, Qiming Sun, Cong Yi, Ayaz Najafov, Hongguang Xia
2022, 13(3): 227-229. doi: 10.1007/s13238-021-00873-4